Quality of life for cancer patients

Özgur Özyilkan

Division of Medical Oncology, Baskent University Faculty of Medicine, Ankara, Turkey
Different diseases may affect different bodily functions and lead to different physical and emotional problems. There is little systemic information on the effect of disease and its treatment on the quality of life (QoL) or psychological adjustment of the cancer patients. Over the last decade, clinicians have accepted that, while survival and disease-free survival are both critical factors for cancer patients, over­all QoL is fundamental. Quality of life is the state of well being that is a composite of two components: the ability to perform everyday activities that reflect physical, psychological and social well-being, and patient satisfaction with levels of functioning and control of the disease. There has been exponential growth in reports relating to the development and evaluation of quality of life measures. All patients with cancer ask themselves a wide variety of questions about their life and future. Measurements of tumor volume and tumor markers are the primary parameters of response to treatment. However, improvements in such measures can produce little, if any, noticeable benefit for the patient or may be associated with a decline in QoL if the side-effect profile of treatment is high. It has become increasingly evident that the impact of disease and treatment on a patient’s QoL is an important measure of effective cancer management. Many types of medical interventions are designed to improve the quality rather than to extend the duration of patients’ life. Improved QoL is an important goal of caring for patients with cancer. Oncologists may concentrate all their expertise on the scientific application of modern oncological knowledge, and sometimes forget that emotional and psychosocial supports are also essential. 

Integrated model of supportive care service: Institute for Oncology and Radiology of Serbia 

F. Djordjevic, S. Bosnjak, J. Dimitrijevc, S. Susnjar, A. Zilic, N. Bakic, M. Andrijic

The Institute for Oncology and Radiology of Serbia, Belgrade, Republic of Serbia
Supportive care makes excellent cancer care possible. Our team has strongly believed that supportive care improves both quality of care and quality of life. The department for supportive oncology of the institute is a part of the Clinic for medical oncology. The Department for Supportive Oncology consists of Intensive Oncology Care Unit and Outpatient Pain Clinic, not only for pain management, but also for the treatment of other symptoms caused by advanced cancer or its treatment. Furthermore, we have a mobile team which provides on-call consultations for hospitalized patients (education and clinical research are also parts of our activities.) Our team consists of 6 physicians, 14 nurses, psychologist, social worker and pharmacist. The main indications for admission to the unit are: severe adverse effects of antitumor therapy, uncontrolled symptoms of advanced disease regardless of the phase of the disease, oncology emergencies and administration of complicated chemo regimens requiring 24-hour monitoring, or administration of chemotherapy in patients who could be expected to develop severe chemotherapy-induced complications. In every day practice, we rely on well known tools such as ESAS list or CTCAE and MASCC, ESMO, ASCO, NCCN guidelines. Inpatient mobile team consists usually of a physician and a nurse. In the past 5 years we had almost 5000 consultations for hospitalized patients on demand of their treating oncologists. The main reason for consultations was uncontrolled pain. Outpatient Pain Clinic is opened every working day for the patients of the institute seeking help in pain relief and other symptoms caused by advanced cancer. In the past five years we had more than 5000 exams and consultations mainly for chronic cancer pain and less frequently for dyspnea and consultations about end of life care. Our motto is “treat the whole patient, not just the disease“, and because of this, our vision is that each patient and family should receive the support and care they need to live with cancer and cope with its treatment.

The efficacy and tolerability of slow-release (SR) hydromorphone in the treatment of cancer dyspnea in lung cancer patients: experience from the Institute for Oncology and Radiology of Serbia (IORS)

F. Đorđević, N. Stanić, J. Dimitrijević, S. Bošnjak, A. Zilić, J. Spasić, S. Šušnjar

The Institute for Oncology and Radiology of Serbia, Belgrade, Republic of Serbia
Introduction. Cancer-related dyspnea and pain are common in patients with lung cancer. Morphine is an effective medication for both symptoms. Oral SR morphine is not available in Serbia. Oral SR hydromorphone is used instead. The efficacy and tolerability of immediate-release (IR) hydromorphone in the treatment of cancer dyspnea was documented in the literature. Objectives. To assess the efficacy and tolerability of oral SR hydromorphone (24-hour release) for the treatment of cancer pain and dyspnea in lung cancer patients. Methods. Twenty-five patients with lung cancer with severe dyspnea and pain (both assessed on 0-10 numeric rating scale) were included. On day 1 (D1) patients were treated with oral IR morphine 5 mg Q4h with the same dose for the breakthrough pain and dyspnea. In all patients who required at least 30 mg of oral IR morphine for a 24-hour period, SR hydromorphone 8 mg was included in the treatment on day 2 (D2) with IR morphine 5 mg for breakthrough pain and dyspnea. On D2-D5, the efficacy and tolerability of SR hydromorphone, as well as adverse effects were monitored. Results. On D1, the mean intensity of dyspnea was 7.48 (SD=0.510). On D5, all patients were still on 8 mg of SR hydromorphone, without the need of morphine for breakthrough pain or dyspnea. On D5, the mean intensity of dyspnea was 2.48 (SD=0.770), with a statistically significant decrease in intensity compared to D1 (p<0.001). There were no registered side effects of SR hydromorphone. Conclusion. The use of convenient SR hydromorphone resulted in sustained relief of dyspnea, as well as pain, with acceptable tolerability.

The favorable prognostic significance of atelectasis in patients with advanced non-small cell lung cancer - results of a prospective observational study

Mircea Dediu, Emilia Crişan, Maria Răduţ, Alin Țârlea, Dragoş Median, Aurelia Alexandru, Georgeta Vremeş, Cristian Gal

Sanador Clinical Hospital Bucharest, Institute of Oncology Bucharest
Purpose. For lung cancer, the TNM staging system included atelec­tasis (At) as a negative prognostic factor, within the T category. However, according to our clinical experience, we observed the opposite. The aim of the study was to evaluate the influence of At on patient outcome for unresectable stage III and IV non-small cell lung cancer (NSCLC). Patients and methods. We prospectively evaluated the patient survival data, in correlation with the presence, At(+), or absence, At(−), of At. A distinct analysis according to stage was preplanned. Univariate and multivariate analysis were performed to refine the prognostic significance of At. Results. We evaluated 1352 consecutively treated patients, during 1997-2004. Sixty-eight patients (5%) were identified with At, of which 46/592 (8%) were in stage III, and 22/760 (3%) were in stage IV. The survival data were significantly better for patients At(+) vs. At(−); median overall survival (OS) was 21 months (95% confidence interval [CI]; 12.37-29.63) vs. 10 months (95% CI; 9.25-10.75) (p< 0.001), and median progression free survival (PFS) was 17 months (95% CI; 11.71-22.29) vs. 7 months (95% CI; 6.48-7.52) (p<0.001). The most consistent difference, favoring patients At(+), was noted for patients in stage III, with OS of 24 months (95% CI; 18.65-29.35) vs. 14 months (95% CI; 12.43-15.57) (p<0.001), and PFS of 19 months (95% CI; 12.11-25.89) vs. 8 months (95% CI; 6.89-9.02) (p<0.001). In stage IV, we noted a non-significant trend toward improved survival in patients At(+); OS: 16 months (95% CI; 4.49-27.51) vs. 9 months (95% CI; 8.51-9.49) (p=0.21), and PFS: 8 months (95% CI; 5.80-10.20) vs. 6 months (95% CI; 5.36-6.64) (p=0.12). The multivariate analysis showed that At, stage and ECOG performance status were independent predictors for survival. Conclusion. At predicts a better survival in patients with advanced NSCLC. The prognostic value is more stringent for stage III patients. The 2016 revised edition of the TMN staging system withdrew At from the non-sized base negative predictors, which is according to our results.

Current status and further perspectives in the treatment of EGFR mutant non-small cell lung cancer (NSCLC)

Mircea Dediu

Sanador Clinical Hospital Bucharest
The discovery of EGFR activating mutations in NSCLC set the biologic ground for the use of EGFR tyrosine kinase inhibitors (TKIs) as specific agents targeting this molecular abnormality. As such various TKIs became widely used in first line setting, important peculiarities regarding efficacy and the side effect profile were noted only recently. From this perspective, first and second generation TKIs may account for clinically significant differences which could impact on the choice of the first-line therapy. The treatment at progression remain challenging as different options are recommended in relationship with the clinical course of disease, on one hand, and the type of molecular resistance, on the other hand. Indolent or isolated distant progression does not mandate for immediate change in the first-line therapy. On the other hand, the documentation of the T790M resistant mutation may request for immediate use of osimertinib, a new agent with a specific inhibitory action. This lecture will present the most relevant differences in terms of activity and side effects of the first line TKIs, the current recommendations for treatment of progressive disease and the most promising developments in this specific therapeutic area. 

Updates in the management of advanced NSCLC

Alexandru C. Grigorescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The current issue nowadays is the integration of biomarkers in the clinical practice for the treatment of non-small cell lung cancer (NSCLC). At the moment, guidelines state that patients with adenocarcinoma should be tested for EGFR mutation and ALK fusion. Now, National Comprehensive Cancer Network (NCCN) guidelines re­com­mend testing adenocarcinoma patients for EGFR and ALK, but also recommend broad molecular profiling to detect more rare muta­tions, including ROS1, KRAS, RET, BRAF V600E, MET and HER2. The use of liquid biopsy in advanced NSCLC is another problem that will be discussed in this presentation. An example is the T790M status as­ses­sed from plasma, urine or tissue. The treatment conducted by bio­markers will be discussed: the initial treatment of a patient with me­tastatic NSCLC and EGFR mutation, treatment beyond progression un­der the TKI. It will also be presented the treatment of a patient with newly diagnosed metastatic ALK-positive NSCLC, with first and se­cond generation of ALK inhibitors. The most important subject is the treatment of a mutation-negative patient with adenocarcinoma and progression on platinum. The treatment for patients with PD-L1 ne­ga­tive (defined as <1%) and PD-L1 positive will also be discussed.

The integration of supportive and palliative care with medical oncology

Alexandru C. Grigorescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The need for integration will be discussed, and also the modality of integration will be reviewed. The ESMO designated Centres Working Group will be also presented, with its aims and prodigious activity. The 13 items necessary to be achieved for a clinic in order to be admitted in the “Community of Designated ESMO Centers” will also be discussed. An example of ESMO Centre for Integration is the Institute of Oncology Bucharest. Despite its activity is blocked at the moment by some unmet needs, the premises of the same center are not too far to be realized. The protocol for investigation of physical and psychological symptoms and social problems was elaborated. Emergency in palliative care will be another protocol with a proposal of approach (serious symptoms that severely affect patients’ quality of life). The criteria for admission to the hospital represent another matter of debate, because of important needs that should be covered by the center. Palliative counseling and treatments in the various departments of the hospital are important component of the designated center. Because there cannot be treated all patients in the same time at the Supportive and Palliative Care Department of the center, some patients with less severe problems (moderate pain, social problems, familial problems etc.) will be consulted by the team of the center and then will be treated in the department where they were hospitalized for chemotherapy, radiotherapy or surgery. They will be on a waiting list, since they can be treated at home by a mobile team, or will be referred to the Supportive and Palliative Care Department, or to the hospice. 

Increased risk of recurrence associated with certain risk factors in breast cancer patients after DIEP-flap reconstruction and lipofilling - a matched cohort study with 200 patients

Sonia Fertsch, Mazen Hagouan, Beatrix Munder, Tino Schulz, Alina Abu-Ghazaleh, Julia Schaberick, Peter Stambera, Mohammed Aldeeri, Oliver Christian Thamm, Christoph Andree

Klinik für Plastische und Ästhetische Chirurgie Dusseldorf, Germany
Background. Lipofilling is performed in breast cancer patients to op­ti­­mize the aesthetic outcome following breast reconstruction af­ter mastectomy. Despite its common usage worldwide, little is known about the interaction of the lipoaspirate and dormant cancer cells. Up to date, no risk factors that increase the risk for cancer re­­cur­­rence have been established. This study aims to identify risk fac­tors for lipofilling candidates after breast cancer and questions the oncological safety of lipofilling in lymph node positive disease. Me­thods. Matched retrospective cohort study: the disease-free sur­vi­val between 100 breast cancer patients undergoing a lipofilling after their DIEP-flap reconstruction and 100 matched control patients with no subsequent lipofilling was analyzed. Further, patients were subdivided according to risk factors, which were categorized as Patient-­Dependent Factors (PDFs) and Tumor-Dependent Factors (TDFs). Disease-free survival and hazard ratios were compared to iden­tify potential risk factors that may increase cancer recurrence. Results. Median follow-up was 76.5 months from the mastectomy, and 31 months from the startpoint to the end of follow-up. Se­ven and eleven patients had recurrence in the lipofilling and con­trol group, respectively, presenting with comparable disease-free survival rates and an insignificant Hazard Ratio (HR=0.57; 95% con­fi­dence in­ter­val; 0.22-1.47; p=0.24). According to subgroup survi­val analysis, li­po­filling increased the risk of recur­rence in women with a positive no­dal status (p=0.035) and a high-grade neoplasia (p=0.049). Conclu­sions. No ge­neral increased recur­rence risk was ob­served between the lipofil­ling and control group. The subgroup analy­sis identified high-grade neo­plasia and positive nodal status to be a risk factor for cancer re­cur­rence. Patients with a known node po­si­tive disease have an increased risk of occult micrometastases in their lymph nodes. Further stu­dies are necessary to clarify whether dor­mant breast cancer cells in form of micrometastases in the lymph nodes can be reactivated by the factors secreted by adipose derived stem cells. 

Imbalance between matrix metalloproteinases and their tissue inhibitors in head and neck squamous cell carcinoma

Adina Elena Stanciu1, Adina Zamfir-Chiru-Anton2, Marcel Marian Stanciu3, Cristian Radu Popescu4, Dan Cristian Gheorghe5

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest, Department of Carcinogenesis and Molecular Biology, Bucharest, Romania 
2. “Grigore Alexandrescu” Children’s Emergency Hospital, ENT Department, Bucharest, Romania
3. Politehnica University of Bucharest, Electrical Engineering Faculty, Bucharest, Romania 
4. Colțea Clinical Hospital, Head & Neck Surgery Clinic, Bucharest, Romania 
5. "Maria Sklodowska Curie" Children’s Emergency Hospital, ENT Department, Bucharest, Romania
Background. The imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) has been proven to be closely associated with a multitude of pathological state, especially tumor invasion and metastasis. The aim of the study was to assess the serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 and MMP-9/TIMP-1, MMP-2/TIMP-2 ratios in head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological characteristics. Seventy patients with HNSCC were evaluated be­fore and 2 days after surgery. Forty healthy volunteers were selected as controls. Results. Preoperative MMP-9, TIMP-1 levels and MMP-9/TIMP-1, MMP-2/TIMP-2 ratios were significantly higher in HNSCC group than in control group (p<0.001, p=0.021, p<0.001, p=0.002, respectively). Changes in MMP-9 concentration and MMP-9/TIMP-1 ratio after surgery had a negative correlation with lymph node involvement (r=-0.35, p=0.021 and r=-0.37, p=0.013), while changes in TIMP-1 had a positive one (r=0.45, p=0.006). Histological grade was positively correlated with the changes in circulating TIMP-2 level (r=0.39, p=0.021). No significant correlation was discovered between MMP-2/TIMP-2 ratio and tumor grade or any clinicopathological variables. Conclusions. Our results suggest that an imbalance between MMP-9 and TIMP-1 could play an important role in metastatic spread via lymphatic pathways of HNSCC cells. MMP-9/TIMP-1 ratio and, in particular, MMP-9, TIMP-1, TIMP-2 may represent suitable biomarkers for early diagnosis or detection of disease progression and dissemination, for estimating prognosis and for predicting treatment response in HNSCC patients. 

The management of hepatocellular carcinoma

Yesim Yıldırım

Anadolu Medical Center Hospital, Medical Oncology Department, Kocaeli, Turkey
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. It is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. 
The etiology of HCC has been reported to be related to a variety of diseases such as hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcoholic hepatitis, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome including diabetes mellitus. The management of hepatocellular carcinoma (HCC) is best performed in a multidisciplinary approach by hepatologists, transplant and hepatobiliary surgeons, medical oncologists and interventional radiologists. 
Asset 1
Asset 2

Immunotherapy and mTOR inhibitors - a new perspective in the treatment of advanced and metastatic urothelial carcinomas

Andreea Lăzescu, Daniela Zob, Dana Stănculeanu, Laura Ciurea, Anca Zgură, Simona Lupu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Bladder cancer is the seventh cause of cancer death in men and the tenth in women. In metastatic disease, the prognosis remains poor, with a median survival of 15 months. Chemotherapy has remained standard systemic therapy over the past 15 years for patients with recurrent or metastatic disease. The therapeutic regimens recommended by guides in metastatic disease, as the first treatment line, are the combination of gemcitabine and platinum salts or the MVAC combination. Currently, there is no second-line standard systemic therapy for patients with tumor relapse after first-line chemotherapy. Therefore, the treatment of advanced and metastatic urothelial tumors remains a challenge for oncologists. Following radical cystectomy, more than half of patients with invasive urothelial carcinoma will develop recurrent disease. The excellent results obtained in the treatment of other solid tumors using targeted therapies such as tyrosine kinase inhibitors or CTLA-4 anti-CTL-4 or PD1 inhibitor immunotherapy have led to the idea that these therapies could be used with promising results in the treatment of metastatic bladder cancer. The acquisition of mutations in the PI3K/AKT/mTOR intracellular signal transduction pathway has been demonstrated in over 40% of bladder cancers, suggesting that blocking the mTOR pathway would be a promising target therapy in this pathology. Starting from this idea, there are currently several phase I and II studies of mTOR inhibitors like temsirolimus or sirolimus, the preliminary results being encouraging. In terms of immunotherapy in metastatic bladder cancer, there are currently several phase I or phase II studies testing anti-CTLA-4 therapy (ipilimumab) or PD1 inhibitors (nivolumab). Besides these molecules, there are studies that test new molecules such as MPDL3280A, MEDI4736 and MK3475 (lambrolizumab). All preliminary data show the efficacy of these new therapies in metastatic urothelial carcinoma. Our paper aims to review these new therapies by presenting the undergoing studies for recurrent and metastatic urothelial carcinoma with the preliminary results and safety profile of these new agents. In the future, we will have a new standard in the systemic treatment of advanced and metastatic urothelial carcinomas.

Therapeutic targets in ovarian cancer

Dana Lucia Stănculeanu, Daniela Zob, Oana Cătălina Toma, Raluca Ioana Mihăilă

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Ovarian cancers are among the most deadly cancers, because only 20% are detected in early stages and only 30% of patients survive at 5 years. These data plead why translational medicine has developed regarding cancer, because a tumor is being considered heterogeneous and a single treatment cannot treat all forms of ovarian cancer. Based on the molecular classification of ovarian cancers, new opportunities for translational medicine have been born. Taking into account the main histological subtypes of ovarian cancer and associated mutations or chromosomal aberrations, the main targets, the appropriate therapy and the clinical implications are analyzed in this presentation.  

Update in mRCC – first-line therapy

Dana Lucia Stănculeanu, Daniela Zob, Oana Cătălina Toma, Raluca Ioana Mihăilă

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Metastatic renal cancer is an important field regarding targeted therapy in oncology. If until the early 1990s we were only talking about im­munologic treatment with high doses of interleukin 2 and alpha-interferon, starting with 2005 and 2006, antiangiogenic therapy appeared in the therapeutic arsenal and two new molecules, sorafenib and sunitinib, were approved for use. R.J. Motzer’s study of sunitinib versus interferon-alpha treatment of naïve patients with metastatic disease and the clear cell carcinoma histological subtype published in New England Jour­nal of Medicine in 2007 resulted in a double progression-free survival (PFS) - over 11 months versus 5 months for sunitinib, with p<0.001, and a convenient toxicity profile. In 2007, bevacizumab was registered in the first line of treatment for the same group of patients, a monoclonal antibody with antiangiogenic effect, following the study of AVOREN and CALGB 90206 (median PFS 10.2 months vs. 5.4 months). In case of “poor risk” renal cancer, the phase III ARCC study established the role of the mTOR inhibitor for this category of patients with an overall survival of 10.9 months and a statistically significant PFS. In 2010, another antiangiogenic TKI inhibitor, pazopanib, was recorded due to VEG 105192 study results, with a 54% reduction in risk of progression or death compared with placebo and a significant increase in PFS in all subgroups of pa­tients. Anticipating the EMA requirement, the COMPARZ study was initiated, a head-to-head non-inferiority study comparing this molecule with sunitinib, because the data showed similar results of the two molecules in terms of effectiveness and safety profile. The results of the registration studies for the two molecules, sunitinib and pazopanib, have been confirmed by real-world data, along with data from the extended access programs. The results of the International Mrcc database Consortium confirmed the clinical results for sunitinb and pazopanib. In conclusion, the treatment line for metastatic renal cancer has remained unchanged from 2010 until now.

Geriatrics and oncology

Gabriel-Ioan Prada, Raluca-Mihaela Nacu, Anna-Marie Herghelegiu 

“Ana Aslan” National Institute of Gerontology and Geriatrics, Bucharest
Neoplasia is a major cause of morbidity and mortality in the elderly. This population group is more likely to develop a neoplasia. Also, old age influences both tumor growth and metastasis. The relationship between cancer and the aging phenomenon is complex, a number of factors being involved: the alterations of anti-tumor defense mechanisms, carcinogen exposure, existing comorbidities, morphofunctional transformations installed with aging. There are a number of theories on how neoplasms develop in the elderly: decreased DNA repair capacity, oncogenes activation or amplification, loss of tumor suppression gene, decreased capacity for immune surveillance, extension of carcinogen exposure period, and increased sensitivity of aged cells at the action of carcinogenic factors. However, there is still controversy about the fact that aging and carcinogenesis are interrelated processes. Some authors state that neoplasia is a consequence of the normal aging process, while others believe that neoplasia and aging would have common aetiological factors. There is a link between chromosomal alterations and neoplasms. A number of congenital conditions accompanied by chromosomal alterations and an increase in malignancies reveal DNA repair and recombination abnormalities, and many genetically-determined syndromes present accelerated aging phenomena and increased neoplasia. The increasing incidence of malignancies with aging can be interpreted based on two theories of aging. The first is the theory of errors that asserts that over time there is an accumulation of alterations in the vital functions of cells and organs, culminating in aging-specific manifestations. Random mutation may occur in certain essential genes or in many genes, cumulated. The multi-stage carcinogenesis model fits this theory because successive neoplasia-generating mutations accumulate during the aging process. Another theory is one of programming, which considers aging to be a final stage of a programmed process that goes from embryogenesis to growth and maturation, and ultimately to progressive degradation. During aging, some genes can be expressed, while others are suppres­sed. On the other hand, an important aspect is related to the complex peculiarities of the elderly patient with neoplasia.

Testicular germ cells tumors in child and adolescent - a clinical study between 1990 and 2015

Monica Dragomir, Codruţa Radu, Monika Bădoi, Oana Iaru, Olivia Drăgnescu, Rodica Anghel, Mircea Savu, Dragoş Mitulescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Introduction. Testicular tumors account for approximately 4% of the solid tumors diagnosed in the child and adolescent. Most cases are germ cell tumors, curable even in advanced diagnosis stages. Study goal. The assessment of clinical particularities and therapeutic outcomes for germ cell testicular tumors in child and adolescent. Patients and method. A retrospective, observational and analytical study conducted between 1990 and 2015. The study group included 36 children with testicular germ cells malignant tumors treated postoperatively in Bucharest Institute of Oncology. Multimodal treatment consisted in surgery plus adjuvant chemotherapy +/- radiotherapy. Follow-up period: at least one year after treatment discontinuation. Results. Two incidence peaks were observed in age groups 0-4 years (17%) and 15-19 years (75%). Histological types: seminoma - 3 patients; non-seminoma - 16 patients (1 teratoma; 1 coriocarcinoma; 3 endodermal sinus tumors; 11 embryonic carcinoma); mixed tumors - 17 patients. Diagnostic stages: stage I - 12 patients, stage II - 14 patients, stage III - 5 patients, stage IV/IIIc - 5 patients. Multimodal treatment consisted in surgery plus adjuvant chemotherapy +/- radiotherapy. Surgical interventions: orchi­ectomy in all cases (27 inguinal, 9 scrotal) plus lymphade­nectomy in 9 cases. Fifteen patients had also undergone radiotherapy. Evolu­tion under treatment. Complete remission - 72.2%, partial remis­sion - 5.5%; stationary disease - 1 patient, continuation of evolution - 13.8%. The overall survival was 82.5% at 1 year and 79.4% at 5 years; stages I and II: 92% survival at one year and 87.6% at 5 years; stage III/IV: 70% survival at 1 year and 58.3% at 5 years. Conclusions. The therapeutic results in the studied group were comparable with those in the reference oncology centers: overall survival was 80% at 5 years and 90% in cases diagnosed in stages I-II.

The use of high doses of morphine in the child with cancer 

Codruța Comșa1, Monica Dragomir2

1. “Prof. Dr. Al. Trestioreanu” Institute of Oncology, Bucharest, Pediatric Oncology, Palliative Care Compartment 
2. “Carol Davila” University of Medicine and Pharmacy, Bucharest
Introduction. Pain occurs in 65-85% of advanced cancer patients and can be controlled in 85-95% of cases using the WHO analgesic ladder. The causes for morphine-(pseudo) resistant pain are: underdosing, disease progression, pain semi-responsive/resistant to opioids, opioid tolerance, associated psycho-emotional aspects. The treatment of morphine-(pseudo) resistant pain is: dose increase, co-analgesic association, opioid rotation, assessment and control of psycho-emotional aspects. Study goal. The assessment of evolutionary particularities of children with pain due to advanced cancer, who needed high doses of morphine (equivalent to ≥5.8 mg/kg/day by oral route). Material and method. We present the cases of 2 children with advanced cancer who needed high doses of morphine. The patients with mixed pain (nociceptive + neuropathic) received morphine up to 7 mg/kg/day and 35 mg/kg/day by oral administration combined with co-analgesics, obtaining unsatisfactory pain control. In the first patient, the dose increase was started, but he died from oncological disease progression before gaining pain control. In the second patient, the morphine route of administration was changed to subcutaneously, with a dose reduction to 9 mg/kg/day, subsequently requiring a rapid increase of the dose to 42 mg/kg/day, with satisfactory pain control. Discussions. The morphine doses used for the presented patients exceed the usual doses mentioned in specialized literature, which is a sign of a pain that is difficult to treat. We have considered: suboptimal doses, increased morphine demand due to disease progression, tolerance, morphine resistance, perturbation of absorption/metabolism of oral administered morphine, and associated psycho-emotional aspects. Strategies for superior pain control were: association of co-analgesics at optimal doses, change of morphine administration route, and rotation of opioids. The observed side effects were minimal: nau­sea at treatment initiation/rapid dose increase, persistent constipa­tion. Conclusions. 1. Morphine is the major opioid of first intention in severe pain due to its ease of administration and its few and mild side effects. 2. In case of apparently morphine-resistant pain, the rotation of opioids should be considered. 3. Changing the morphine route of administration is an easy and effective method to get better pain control using the same substance.

Malnutrition and neoplastic cachexia in pediatric oncology

Monica Dragomir, Codruţa Comşa, Monika Bădoi, Oana Iaru, Olivia Drăgnescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Data from specialized literature suggests that 46% of children with malignancies have secondary malnutrition as a result of numerous tumors or oncological therapies. It is recognized that impairment of nutritional status is a factor contributing to the decreased immune function, delayed wound healing, and metabolic disorders, and implicitly influencing the prognosis of the disease. Malnutrition in children and adolescents with cancer is reported as common or absent at the time of the diagnosis. Studies report rates between 0 and 50%, depending on the type of cancer. Recent data suggest that malnutrition varies depending on the type of malignancy, disease status, metastatic status and toxicity of multimodal cancer therapies. Most cancers benefit from multimodal treatment, surgery, radiotherapy and poly-cytostatic chemotherapy protocols, with side effects that can lead the child to a state of malnutrition. Furthermore, combined therapies may lead to potentiation or synergism of adverse effects. Undernutrition has an important prognostic role of survival in child cancers, especially in children with solid tumors in metastatic stages. Nutritional therapy strategies are indicated for all affected children, starting at the diag­nosis of cancer, in order to prevent and/or correct growth and development disorders before the overall condition and nutritional status are severely compromised. Appropriate nutrition during malignancy plays a crucial role in the response to treatment and in the quality of life. Conclusions. 1. Nutritional intervention strategies should be part of the supportive therapy plan. 2. Malnutrition in the child with cancer should not be accepted at any stage of the disease or tolerated as an inevitable process.

Study on the variation at the level of the serum glycoproteins and of the metalloproteinases during the development of the Walker-256 carcinosarcoma 

Daniela Glăvan, Maria Iuliana Gruia, Valentina Negoiţă

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Because cancer is the second common cause of mortality in the civilised world, the identification of new tumour biomarkers is especially important in early detection, the monitoring of treatment, the occurrence of the relapses and in the development of metastases. Among the serum glycoproteins involved in cancer, we have studied the variation of the level of the serum sialic acid in the development of the Walker-256 carcinosarcoma. At the same time, we have studied the serum concentra­tions of the metalloproteineases MMP-2 and MMP-9, after 12 consecutive treatment series with doxorubicin. It was noticed that the serum values of the sialic acid and of the MMP have had the tendency to gradually increase at the same time with the growth of the tumour. Following the treatment, these values came back to normal, but they increase again with the relapses and/or the occurrence of the metastases. To conclude, the determination of the serum sialic acid and of the metalloproteinases represents parameters useful for early detection and the development of metastases. These observations together with the identification of new functions of the metalloproteinases in the early stages of cancer led to a reformulation of the MMP inhibition strategies. A better understanding of the complex nature of this proteolytic system and global approaches for the identification of relevant MMP which should be targeted for each cancer patient will be necessary in order to clarify if the MMP inhibition may be part of the future therapies against cancer.

The mechanisms for the production and monitoring of the oxidative stress in the dynamics of the tumour growth

Maria Iuliana Gruia, Mirela Dumitru, Valentina Negoiță, Daniela Drăgoi, Cristina Nițu, Mariana Saulea

“Prof. Dr. Alex. Trestioreanu” Institute of Oncology Bucharest
The reactive oxygen species (ROS) are produced as a consequence of the normal aerobic metabolism. Among these, the free radicals are usually remetabolised or inactivated in vivo by an entire group of antioxidants. The individual members of the group of antioxidant are specialised in the prevention of the generation of ROS, in order to destroy the oxidating potential or to capture them. Under physiological conditions, the tissue attack induced by the oxidative stress is minimum. A relative or absolute deficit in the antioxidant defence may determine the increase in the oxidative stress, and this event is associated both with the causes and the consequences of certain pathologies, including also cancer. The purpose of the paper is to identify the signalling role of the ROS producing systems and the activation of the endogenous anti­oxidant defence for the purpose of reducing the oxidative stress in the dynamics of the growth and development of malignant tumours. Our in vivo study was performed on models represented by the Wistar rats carriers of experimental tumours, the data being extrapolated within clinical trials made up of patients with breast tumours, in the dynamics of the surgical treatment and radiation therapy. The paper falls within the category of translational research and presents data initiated in our lab by going through all the stages from the adaptation of biochemistry techniques and their validation on experimental models up to their introduction within clinical practice. The results obtained indicate the utility of the biochemical parameters of oxidative stress in the monitoring of the evolution and efficiency of oncological treatment.

Comparative analysis of EGFR expression within the bladder cancer in humans and dogs

Mirela Dumitru1, Mirela Mihăilă2, Camelia Mia Hotnog2, Monica Horțopan3, Lorelei Irina Braşoveanu2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. “Ştefan S. Nicolau” Virusology Institute, Bucharest
3. Fundeni Clinical Institute, Bucharest
The study of the bladder cancer on animal models is essential for the improvement of the management of this disease. Bladder cancer represents 2% of all cancers, both in humans and dogs. The bladder tumours occurring spontaneously in dogs are similar from a histopathological perspective, from the point of view of heterogeneity, of the tumour sites and the response to conventional therapy to the ones affecting humans, and this is why they can be a relevant model for bladder cancer. The molecular characterisation of the canine urothelial carcinomas may optimize the relevant model for bladder cancer. The Epidermal Growth Factor Receptor (EGFR) tyrosine kinase receptor expressed in the majority of the tumour cells is involved in the cellular proliferation, tumour progression and development of metastases, and it is also a target in cancer therapy. The paper presents the EGFR expression in the human urothelial carcinomas compared to the EGFR expression in the tumours occurring spontaneously in dogs (from the literature data).  The EGFR receptor expressed frequently in the human tumour cells has a structure which is almost identical to the one of the receptor expressed in the canine tumours. The EGFR overexpression has been noticed in over 73% of the invasive urothelial carcinomas, both in humans and dogs. The high expression of the EGFR receptor associated significantly (100% specificity) with canine urothelial carcinomas might be a marker for the diagnosis of the bladder tumours in dogs. The study of the anti-EGFR therapies in the veterinary oncology clinic might offer new perspectives in the biology of the bladder cancer, the clarification of the resistance mechanisms or the efficiency of the new targeted therapies.

Current indications of different types of mastectomies in breast cancer treatment

Cristian Bordea, Alexandru Blidaru, Elena Ichim, Bassam El Houcheimi

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The 20th century witnessed a continuous series of changes in breast surgery. In the last century, the Halsted radical mastectomy used to be the standard surgical procedure in breast cancer (over 90%). Gradually, the Halsted procedure was replaced, towards the end of the seventies, by modified radical mastectomy techniques. Following that time interval, the Madden type modified radical mastectomy began to be the most frequently used technique, so that it is still accounted for more than three quarters of all surgical operations for breast cancer in Romania. Since 1999, we have performed post-mastectomy breast reconstruc­tion. In these cases, the modified radical mastectomies were replaced with the same oncological safety results by skin-sparring and nipple sparring mastectomies. All these confirm that our diagnosis and therapeutic standards have been aligned with the European ones and stand proof to the major changes going on in breast surgery.

Difficulties in preoperative localisation and surgical biopsies of non-palpable breast cancers

Cristian Bordea, Alexandru Blidaru, Bassam El Houcheimi, Elena Ichim

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Mammographic screening, enhanced mammography resolution, as well as advances in breast ultrasound examination and MRI have resulted in the increasingly more frequent identification of small suspect mammary lesions that do not have a clinical expression. Infraclinical mammary lesions discovered on mammography/ ultrasonography/ MRI raise problems with respect to an appropriate approach. Diagnosis and treatment of such lesions require their pre-operative localiza­tion. We consider surgical excision to be a good method of approach in such lesions. Full excision of the lesion enables complete histological examination and immunohistochemistry, ensures right diagnosis, and curative surgical intervention can be performed within the same operative time. In the absence of pre-operative localization of such lesions, the surgeon is put in the situation of operating an image that has no clinical expression. Unless the lesion is localized preoperatively, surgical excision is performed blindly, as the lesion is difficult to identify. Pre-operative localization provides guidance for surgery, ensures the mammographically identified lesion is removed and helps avoid large, unnecessary mammary resections.

The results of 15 years of oncoplastic surgery at the Institute of Oncology Bucharest

Alexandru Blidaru, Cristian Bordea, Mihaela Radu, I. Matei

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The 20th century witnessed continuous changes in breast cancer surgery. Surgical treatment has evolved mainly due to a better understanding of the natural evolution of cancer, increased efficacy of the other antineoplastic therapies, early disease detection, and also the desire to improve the quality of life for cancer patients. As well as many surgical oncology principles which have emerged from breast cancer surgery, the beginning of the 21st century marked the developement of breast cancer oncoplastic surgery. This paper aims to present the results of 15 years of oncoplastic surgery at the Institute of Oncology Bucharest, as well as the indications and techniques from these procedures. Nowadays, at the Bucharest Institute of Oncology, we perform infraclinical breast lesion surgery, vacuum assisted breast biopsy, sentinel node detection and biopsy, breast conserving surgery and skin-sparring mastectomies, as well as breast reconstruction techniques using implants or autologous tissue. All of the above assert that we are in line with the European diagnostic and treatment guidelines and shed light on the major changes that have affected breast cancer surgery. The results show that postmastectomy breast reconstruction using implants delivers a good cosmetic outcome, while at the same time assuring local control of the oncological disease. Immediate breast reconstruction helps patients maintain a positive self image, reducing the psychological trauma associated with breast cancer.

The multimodal treatment prospectives of rectal cancer

Marian Augustin Marincaș, Virgiliu Mihail Prunoiu, Sânziana Ionescu, Eugen Brătucu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The authors raise two problems which occur following the application of the current multimodal treatment protocol for rectal cancer. The first problem mentioned results from the fact that current treatment guide establishes the neoadjuvant radiation therapy indication for the pa­tients with T3 and M0 tumours. The application of this behaviour may represent a disadvantage for the patients with tumours with reduced response to the radiation and chemotherapy and the marked ten­dency for generating metastases, through the delay of the application of the other treatment methods. Although currently there are identified immunohistochemical and genetic markers which offer data regarding the resistance of tumours to radiation and chemotherapy and the risk for the development of metastases, these did not come into the clinical diagnosis and treatment practice. Another problem raised by authors is that of patients with a complete response to neoadjuvant radiation and chemotherapy for which the current treatment protocols do not mention the principles which are meant to include the patient within a follow-up treatment of the type “wait and see”. Thus, complications specific to rectal surgery are avoided. Based on our experience and data in the specialty literature, we could draw up criteria which should allow the inclusion of the patient in such a therapeutic behaviour.

Laser in thoracic pathology

Mihnea Davidescu, Natalia Motaș, Corina Bluoss, Ovidiu Rus, Bogdan Tănase, Olivia Arhire, Teodor Horvat

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The laser technology is used in multiple applications in thoracic surgery from metastasectomies with maximum preservation of lung parenchyma, to lung resections, to the recovery of the interlobular fissure, haemostasis and up to applications in the interventional bronchology, at the border with pulmonology, in disobtructions, ablations of intrabronchial tumours. The advantages of laser are well known: flexible, yet powerful coagulation areas, good hemostasis and aerostasis, high precision in application with reduced damage and maximum preservation of to the lung parenchyma. This paper presents our experience in using the Nd:YAG Limax laser during one year, with 86 surgery patients.

Tumour size, an important factor in the locally advanced lung cancer management

Ovidiu Rus, Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Olivia Arhire, Bogdan Tănase, Teodor Horvat 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Lung cancer currently represents the main malignant disease, based on its frequency, in the entire world. At the moment of the diagnosis, 55% of the patients present metastases, approximately 30% with locally and regionally advanced disease and only 15% in localised stages. The size of the tumour lesion in the locally advanced lung cancer represents an important factor in the management of neoplasm. The study performed in our clinic covered 223 cases diagnosed with locally advanced lung neoplasm in which the size of the tumour and its impact upon the evolution of the disease and treatment were analysed. Correlations between the size of the lesion, survival, the histologic type and the metastases at the level of the lymph nodes have been uncovered. Data resulted confirmed the results obtained in other literature studies, and they also bring new information in the field.

Psychological and clinical considerations in female patients with breast neoplasm

Mariana Pîrgaru

Ambulatory - Psychology Practice
Cancer may be considered one of the great social phobias both through the devastating consequences affecting multiple systems and through the true psychological “mutilation” that patient suffers. An unanimously accepted idea is that the person diagnosed with a malignant tumour manifests and has a wide range of feelings, cancer being a complex disease associated with distress and profound anguish. Women with breast cancer sur­vive with the burden of their disease, of the treatment, of the psycho-social consequences of the disease, all of these contributing to the experience of a serious psychological suffering which implies the adaptation to the status of a cancer patient, to the existential dimension of the disease, the relation with the family, the search for spiritual or religious belief which should offer her moral support and an explanation of the meaning of life and death. The psychological issue of the oncology patient is as follows: the shock of the diagnosis; the process of understanding the medical part; fear of death; inner transforming process in which many of the previous values and be­liefs change; unresolved emotional trauma generating the occurrence of the disease; anxiety lashes out on the neuro-endocrine system of the body, resulting in the increase in the stress hormones and the decrease in immunity. The preservation of the quality of life of the ill female patients at a higher and functional level requires the setting of measures for the improvement of the psychological and emotional status, of the cognitive and social function level, of fulfilling social roles.

The role of transbronchial peripheral biopsy in the diagnosis of lung tumours

Natalia Motaş1, Mădălin Ţeţu2, Florina Vasilescu3, Mihnea Davidescu1, Veronica Manolache1, Alin Burlacu1, Robert Nicolae1, Vlad Alexe1, Mădălina Cioalcă-Iliescu1, Teodor Horvat1

1. Thoracic Surgery Clinic, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. Bronchial Endoscopy Lab, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
3. OncoTeam, Anatomical pathology, Bucharest Monza Hospital, Romania
The histopathological and immunohistochemical diagnosis represents an essential stage in the management of lung tumours. Bronchoscopy is compulsory - it offers data regarding tumour extension and may lead to histo-/cytological diagnosis. When the endobronchial tumour expression is missing, the transbronchial biopsy at the level of the tu­mour may offer the tissue necessary for histological typing. The method is rarely used and usually guidance is performed through one of the following methods: fluoroscopy, computed tomography, endobronchial ultrasound, electromagnetic navigation. Through these guidance methods, the transbronchial biopsies has a rate of success, according to literature, of 62-77%. In the Thoracic Surgery Clinic of the Bucharest Oncology Institute, in the period January 2015 - February 2017, we per­formed peripheral transbronchial biopsies in 36 patients with an imaging diagnosis of lung tumour, without histopathologic diagnosis. Biopsies have not been guided during the procedures, using as a reference only the pre-procedure CT guidance. The histopathologic diag­nosis could be stated based on tissue appropriately collected from 26 patients. The diagnosis rate for the tumoral transbronchial peripheral biopsies performed in this period is 72.22%, an excellent value considering that biopsies have been performed without any guidance method.

Lung cancer: guidelines compared to real life experience

Natalia Motaş, Mihnea Davidescu, Corina Bluoss, Ovidiu Rus, Elena Jianu, Teodor Horvat

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Lung cancer holds the number 1 position among the deaths caused by cancer in the entire world, and the annual number of deaths is constantly increasing. At the moment of the diagnosis, only 10-15% of the patients are in a resectable stage, with potential chances of healing. For a patient suspected of lung cancer, the first step is the complete staging: of the tumour itself, of the dissemination of the local and regional lymph nodes, and of the remote metastases. Then the patient is treated with the means appropriate for the stage of the cancer. For each stage, there are guidelines and recommendations, which in­clude methods and means sometimes inaccesible to our patients due to various reasons. An example in this sense is that too many times complete staging and histopathologic diagnosis represent the responsibility of the thoracic surgeon and not that of the specialists in pneumology. Another example is the almost complete lack of EBUS-TBNA (ultrasound guided transbronchial node puncture) and the need for replacing it with mediastinoscopy, so that the mediastinal lymph nodes can be staged. Thus, the tasks of the thoracic surgeon are not only those of operating resectable patients, but also of contributing constantly to the diagnosis and staging of the majority of the patients. The paper approaches in a realistic manner the differences between the applicable guides and the real possibilities of diagnosis, and it also shows the results obtained in the clinic.

Atypical onset of non-small cell lung cancer with inguinal node and obturatory metastases. Case study

Laura Rebegea1,2, Iuliana Ivan3, Dorel Firescu4,5, Mihaela Dumitru1

1. Radiation Therapy and Medical Oncology Department, “St. Ap. Andrei” County Clinical Emergency Hospital, Galaţi, Romania
2. Clinical-Medical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galaţi, Romania
3. Medical Oncology Department, “St. Ap. Andrei” County Clinical Emergency Hospital of Galaţi, Romania
4. Surgery II Clinic, “St. Ap. Andrei” County Clinical Emergency Hospital of Galaţi, Romania
5. Clinical-Surgical Department, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galaţi, Romania 
Non-small cell lung cancer represents approximately 80-85% of the lung cancer cases. It is the most frequent malignancy following skin cancer. The therapeutic options for stage IV take into account histology, molecular traits, age, performance status, comorbidity and, last but not least, the patient’s preference. We present the case of a 73-year-old patient, who is a smoker, presented in May 2016 and treated at the Clinical Emergency Hospital “Sf. Ap. Andrei” Galaţi, whose first onset sign has been the inguinal and left obturatory metastases, subjected to biopsy, with histology of metastases of malignant melanoma. The immunohistochemical tests have shown a non-differentiated carcinoma with a pulmonary starting point – Ck7(+), TTF1(+). With imaging (CT) for thorax and abdomen and pelvis, no space replacing processes were shown, at the intrapulmonary level, with the presence of the left mediastinal obturatory and inguinal adenopathies. From the personal pathological history, we retain the basal cell carcinoma in the lumbar region, subjected to surgery in 2009. Chemotherapy and palliative radiation therapy were initiated, with the remission of the obturatory and inguinal adenopathies, and at 9 months from the diagnosis, the PET-CT examination showed the primary lung tumour located in LSD. Currently, at one year after the diagnosis, the patient is alive and undergoing palliative chemotherapy. The presented case has raised issues regarding diagnosis and treatment, being a challenge for the multidisciplinary team, mentioning the reduced amount of data in the specialised literature regarding the cases of primary tumours located over the diaphragm, which generate metastases in the inguinal lymph nodes.

Trends in the treatment of solid tumours in patients monitored via imaging 

Iolanda Dumitrescu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Introduction. The Response Evaluation Criteria in Solid Tumours (RECIST) represent a set of norms drawn up by an international consortium made up from the European Organisation for Research and Treatment of Cancer and two national oncology institutes in America. The standardised approach for measuring the solid tumours allows the specifying of the manner of assessing the treatment response in an objective manner, of changing the tumour volume in adult and child patients included in clinical trials. Methods. According to RECIST, efficient and reproducible methods for the investigation of the response to treatment of solid tumours are mainly CT and MRI imaging. In each of the images, by considering the multi-level threshold values, isocontours are shown. The interactive selection of the contours of the tumour and the viewing of the volume through an indirect representation technique or a representation of the isosurface allow the interactive spatial investigation of the analysed structure. Taking into account the imaging resolutions, the surface area of the tumour is determined in each section, total surface area and tumour volume. Outcomes. The recovery of the 3D vi­sual representation allows the exploration and evaluation of the tumour. The objective and timely assessment of the change in the volume of the tumour contributes to the monitoring of the treatment response. The results applied in the clinical assessment of the efficiency of the anti-neoplastic treatment define if the treatment response is favourable, stable or unfavourable. Conclusion. The follow-up of the neoplastic disease may be performed through repeated imaging studies, based on which decisions can be made regarding the continuing of the treatment, taking into account objective and symptomatic criteria. The change and the quantification of the volume of the solid tumours represent an important feature in the clinical assessment of the tumour response to the antineoplastic treatments. It may be mentioned in an objective, efficient and reproducible manner if the patient’s response to treatment is complete or partial, and if the disease is progressing or is stable. RECIST is considered a standardised measure for the assessment of the treatment response of solid tumours. The technological progress in imaging and according to prospective analyses, RECIST is to be extended from the single dimension anatomical assessment to the volumetric and functional anatomic assessment.

Interventional treatment of uterine solid tumours

Monica Cîrstoiu1, Bogdan Dorobăţ2, Mihai Dumitraşcu1, Octavian Munteanu1,3

1. Obstetrics-Gynaecology Clinic of the Bucharest Emergency University Hospital, “Carol Davila” University of Medicine and Pharmacy
2. Interventional Angiography Department of the Bucharest Emergency University Hospital
3. Anatomy Discipline, “Carol Davila” University of Medicine and Pharmacy
Uterine polyfibromatosis is one of the most common solid tumours of the uterus. Regarding the therapeutic options, especially for young female patients, the embolization of the uterus arteries is a minimally invasive, efficient procedure with a reduced rate of secondary reactions. The embolization of the uterus arteries is an interventional technique, with increased efficiency in reducing and even in stopping the haemorrhage in female patients with FIGO IIIB or IV staged cervical neoplasm, playing an important part in increasing the quality of life. We present our experience in the interventional treatment of solid uterine tumours, taking into account that during the period 1.01.2013 - 31.12.2016, at the Obstetrics-Gynaecology Clinic of the Bucharest Emergency University Hospital, the embolization of uterine arteries for haemostatic purposes was performed in 23 female patients diagnosed with cervical neoplasm staged IIIB or IV and in 882 female patients with uterine polyfibromatosis.

Difficult personalities in the relationship between physician and patient

Oana Dumitraşcu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The physician-patient relationship is a complex interhuman relation which starts in an unequal manner through the request of the patient, a person who is suffering, based on his/her need for health, towards another human being, the physician, invested with the authority and the necessary knowledge for relieving his/her suf­fering. This inequality has thus two components, the solicitude and the emotional one. The emotional aspect manifests bilaterally, on the one hand on the part of the patient who invests the physician with his/her physical and psychological care regarding the illness, and on the other hand, on the part of the physician. This emotional transfer is based on the relational matrix formed in the small childhood within the familial relations with the paternal figures who took care of the child. The role conflicts within the physician-patient relationship are based on the psychological resistance of the patient to authority in the context of the disease, which overlaps the educational, experience-related, personality-related and status-related perspectives. Thus, certain patient types are predisposed to difficult relationships: the demonstrative patient, the anxious patient, the depressive patient, the obsessional patient, the narcissistic patient, the paranoid patient, the antisocial patient.

Diagnosis program in the endometrial cancer

Roxana Elena Bohîlțea, Alexandru Baroș, Natalia Ţurcan, Monica Mihaela Cîrstoiu

“Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest Emergency University Hospital
The incidence of endometrial cancer reported in Romania for 2015 was 8.7/100000 women, holding the third position in the genital area, following cervical and ovarian cancer. The current national statistical studies and the ones performed within the Bucharest Emergency University Hospital certify that 35% of the endometrial cancers diagnosed based on the abnormal uterine bleeding are in advanced stages, with a significantly reduced life expectancy. The identification of endometrial cancer should be based on the following items: correct investigation of abnormal uterine bleeding occurring in premenopause or postmenopause, investigation of abnormalities of the cervical cytology examination, diagnosis, treatment and appropriate monitoring of the precursor endometrial lesions or associated with endome­trial cancer and the screening of the increased risk population (Lynch syndrome, Cowden syndrome). The assessment of the risk population and of the cases confirmed in a histopathological manner should be performed in a standardised manner, the medical practice guidelines of the Ministry of Health should be updated and implemented in hos­pitals and in specialised practices and family physicians’ practices; medical practice should focus on early detection, the addressability of women in the early stages of the disease should be improved and the informational system necessary for controlling the route of the cases should also become functional together with the national register of cancer and of rare diseases. The purpose of the performed program is the reduction of mortality owed to cervical cancer, the extension and increase in the quality of life of the female patients through the early identification of this illness.

The use of the immunocytochemical markers in the assessment of risk for cervical precancer 

Alexandru Baroş, Vanessa Andrada Păun, Roxana Elena Bohîlțea, Monica Mihaela Cîrstoiu

“Carol Davila” University of Medicine and Pharmacy Bucharest, Bucharest Emergency University Hospital
The dual p16/Ki67 immunocytochemical coloration, which combines a high sensitivity with high specificity, is the solution which has been developed lately for the optimization of the identification of the precancer of the cervix. The test is a double immunocytochemical marking simultaneously in the same cell for p16 (marker of the transforming infection) and Ki67 (marker for proliferation). Through this immunocytochemical test, the optimization is taken into consideration for the surveillance or sorting of the young female patients with the ASC-US cytological results with high risk of HPV or LCIL, thus avoiding the colposcopies and the eventual invasive gestures in nulliparous women, reducing the anxiety of the female patients related to the colposcopy indication and finally the reduction of the diagnosis costs. At a worldwide level, each year, more than 500,000 new cases of cervical cancer are diagnosed and the average rate of survival at 5 years of patients is only 50%, and thus the introduction of the CINtec PLUS test in the screening programs for cervical cancer may be considered an innovative strategy in the prevention of the cervical cancer and may bring a real benefit to the clinicians and patients through the fact that it helps in identifying the basic illness, establishing that category which implies additional procedures (colposcopy). 

Effects of lidocaine in the perioperative intravenous administration in the cancer patient

Adriana Bene, Carmen Pantiș, Sorela Rădoi 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Objectives. This position proposes a brief presentation of the literature data which support the preoperative use of lidocaine in the oncology patient, followed by the exposure of the results of a randomised prospective study performed between January 2017 and March 2017 in the Institute of Oncology Bucharest. This analysed the effects of xylin in combination with propofol and fentanyl anesthesia upon the immediate post-anesthesia period. Work methods. We have included in the study 58 female patients aged 25-65 years and with a risk ASA I-II proposed for elective mastectomy whom we grouped in two batches. The 28 ill women in batch A have received 1.5 mg lidocaine/kg body weight in bolus prior to the incision followed by continuous infusion with 1.5 mg/kg body/hour and total intravenous anesthesia with propofol, atracurium and fentanyl, ensuring BIS (bispectral index) between 40 and 60. After the surgery, the female patients of this batch received multimodal analgesia at the same time with the conti­nuous administration of lidocaine 0.5 mg/kg body weight/hour. Batch B included 30 subjects whom were administered balanced anesthesia with sevoflurane, fentanyl and tracrium and multimodal analgesia. For the statistical analysis of the results, we have used the Student test, the GraphPad program and the Pearson Chi square test. Results. In batch A, the average dose of tramadol was 150 mg, while for batch B this was 228.3 mg (p< 0.0001; CI between -102.15 and -54.13). The morphine demand was more reduced in batch A. The average duration of waking was 4.03 minutes for batch A and 6.41 minutes for batch B (p<0.0001). Postoperative nausea and vomiting were present in 3 cases from the first group and in 14 cases from the second group (p=0.002649). Conclusions. Total intravenous anesthesia in combination with conti­nuous lidocaine infusion determines the reduction in the consumption of opioid analgesics, more rapid waking and the reduction in the rate of postoperative vomiting.

Investigation of the anaemic syndrome in the neoplastic patient

Mihaela Hrisanta Scarlat, Laura Aifer Calustian

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
As in the current practice anaemia is defined through the reduction in the values of the parameters which assess the quantity of circulating red blood cells, the volume (Ht) and their content in haemoglobin, the primary investigation compulsory in all cases in which we suspect the presence of anaemia is the full blood count. Taking into account the frequency of anaemias considered secondary in oncologic pathology, we performed a retrospective study on 250 patients admitted into the “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest between November 2010 and November 2016, on whom investigations were performed for establishing the diagnosis of anaemia. All patients included in the study were diagnosed with a malignant disease. We monitored the following hematologic parameters: complete blood count with differential, spinal puncture and biochemical parameters: serum iron level, ferritin, LDH, bilirubin, urobilinogen. Only 62% had complete investigations, 42% did not have a peripheral blood smear performed. Spinal puncture could guide the diagnosis in 70% of the cases. The results show the need for observing the diagnosis algorithm, the correct identification of the type of anaemia being essential for determining the appropriate therapeutic attitude.

Endometrial cancer - case study

Mihai Cristian Dumitrașcu, Cătălin George Nenciu, Octavian Munteanu, Monica Mihaela Cîrstoiu

Obstetrics-Gynaecology Department, Bucharest Emergency University Hospital, Romania
Endometrial cancer holds the fourth position from the frequency perspective reported to the total types of cancer in women, estimating that it caused over 8,000 deaths in 2011. Its incidence is increasing with a 3% risk during the entire lifetime. Unfortunately, the survival rate at 5 years is lower than 30 years ago (88% in 1975, 84% in 2006 and 82% in 2011). Though the majority of endometrial cancer cases are diagnosed at an early stage, the differences between the histopathologic features and the particular aspects of the female patient have an impact upon the prognosis and may change the therapeutic approach. In this paper we want to present the case of the patient C.M., aged 66, who presents urgently due to abdominal pain and minimum metrorrhagia. The anamnesis shows that the patient is known with endometrial adenocarcinoma diagnosed 9 years ago and subjected to radiation therapy in a dose of 50 Gy. From the end of the treatments up to this moment, the patient has not come to the physician’s practice. Among the comorbidities, we are mentioning obesity, diabetes mellitus and high blood pressure. This time, the surgical treatment of this pathology was chosen with the histopathological result at 9 years from the first diagnosis of moderately endometroid endometrial adenocarcinoma differentiated with squamoid areas and micro-foci of endometrial carcinoma with clear cells, invasive in the external half of the myometrial wall, with metastases in the lymph nodes (staging pTNM III C2 T1 N2). In this case, we can discus about the existence of the typical comorbidity scheme which determined a status of hyperesterogenism associated with a metabolic syndrome, having a significant survival period after the first diagnosis, although only radiation therapy was performed.

Surgical approach of lung metastases in colorectal cancer

Alin Burlacu1, Corina Bluoss1, Natalia Motaș1, Codruț Stănescu2, Alexandru Martiniuc2, Irinel Popescu2, Teodor Horvat1

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. Fundeni Clinical Institute, Bucharest
Objective. Between 40% and 60% of the patients with colorectal cancer develop metastases, the most common locations being represented by liver and lung. Between 5% and 15% of the patients diagnosed with colorectal cancer develop lung metastases. Without treatment, patients with lung metastases of colorectal origin have an average survival of approximately 10 months and a survival at 5 years under 5%. We present the current aspects of managing patients with colorectal lung metastases and the experience of our clinic in lung resections of metastases of colorectal origin. Materials and methods. A retrospective study was performed in our centres between January 2005 and January 2016. All patients subjected to procedures for lung metastases of colorectal origin have been included in the study. Results. Eighty-three surgeries for lung metastases of colorectal origin were performed in 78 patients. Data regarding age, gender, type of procedure, number of metastases, type of resection, morbidity, mortality and postoperative follow-up are presented. Conclusions. Although up to this moment, there is no randomised study clearly showing the benefit of the resection of the lung metastases of the colorectal cancer, there are multiple papers showing the feasibility and benefit of the surgical treatment with a remedial purpose for a certain category of patients. The selection of the patients who may benefit from the surgical treatment of the lung metastases should be set within a multidisciplinary context, in centres experienced in the management of patients with stage IV colorectal cancer.

Multiple primary neoplasias - a challenge, one patient, four cancers

Alin Burlacu, Natalia Motaș, Alexandru Stoian, Robert Nicolae, Veronica Manolache, Teodor Horvat

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Objectives. The number of patients developing multiple primary cancers, synchronous or metachronous, has been increasing during the last couple of years. Literature considers that this increase is due to the development of the medical diagnosis techniques, the treatment and monitoring of neoplastic patients, known as having a higher risk of developing a second neoplasia compared to the risk of the general population; the increase in the average life expectancy of modern population is also added to such. Description. We present the case of a 73-year-old Caucasian patient, former smoker for 15 years, diagnosed in January 2016 with a routine CT scan, with two lung lesions in the upper right lobe. The pathological history of the patient shows two synchronous neoplasias of cecum and descending colon treated radically: sequential resection and adjuvant chemotherapy. After a disease-free period of 8 years, in January 2016, two spiculiform lung lesions are discovered in the upper right lobe, suspected of being tuberculosis lesions. The patient had undergone tuberculostatic treatment for 5 months, under which it was discovered that the lung lesions grew. After a PET-CT reassessment, which notices the increased metabolic activity of the lung lesions, a surgical treatment is decided - LASER assisted non-anatomic resection. The extemporaneous histopathological examination shows a carcinomatous infiltration for both lesions, but the parafin histopathological examination shows two different results: lung squamous carcinoma and lung metastasis of malignant melanoma – results confirmed by the immunohistochemical analysis. The dermatologic examination uncovered a melanomatous lesion in the nail bed in the second toe of the left foot, for which the resection of the intermediate and distal phalanges was performed. The histopathological examination confirms a Clark stage III malignant melanoma. Conclusions. We consider that the association of two synchronous cancers of colon with a metachronous lung cancer and an oligometastatic melanoma is rare, and has not been reported in literature according to our knowledge. Due to the increased risk of developing a second malignancy, patients with neoplasias require long-term follow-up, and the cases with multiple malignancies are subject to a customised multimodal treatment plan. 

Therapeutic value of internal treatment in the therapy of endometrial neoplasm

Amalia Constantinescu, Lucia Elena Enciu, Raluca Vasile, Veronel Ivaşc 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Brachytherapy plays a major role in the therapeutic management of female patients with neoplasms in the pelvic area. This paper in­tends to show a case study based on the use of the Miami applicator in internal irradiation of the endometrial neoplasm. The Miami applicator offers the chance of a better distribution of the dose in the tumour and a higher protection for the risk organs (bladder and rectum). The adopted irradiation technique is 2D brachytherapy. The applicator reconstruction is made based on X-rays determining its position. When in the appropriate position, the reconstruction begins. A 2-3 mm error in the applicator reconstruction may lead to a dose error of approximately 10%. The female patient aged 60 is internally irradiated 2 times a week, with 500 cGy per session, up to a total dose of 45 Gy. After the comple­tion of irradiation, the female patient is treated surgically. The irradia­tion results are shown following the histopathological result.

LASER lung metastasectomies - assisted following testicular teratocarcinoma

Veronica Manolache, Natalia Motaş, Mădălina Iliescu, Vitalie Rotari, Teodor Horvat

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
We present the case of a 26-year-old patient, with operated testicular teratocarcinoma (radical left orchiectomy), with a result at the histopathological and immunohistochemical examination of mixed tumour with testicular germinal cells (a majority component of immature teratoma, important components of Yolk sac tumour and embryonal carcinoma, limited area of classic seminoma) who benefited from polichemotherapy following the resection of the primary tumour, non-responsive to treatment, developing secondary retroperitoneal and renal left determinations subject to surgery (left nephrectomy) and secondary hepatic determinations subject to surgery (II-III hepatic segmentectomy). In the following examinations the patient is discovered with secondary bilateral lung determinations, with an increase in their size, from one check to the other. Surgical two-stage treatment is performed. The first stage consists in LASER-assisted left lung metastasectomias, with the resection of four metastases in the upper left lobe and four metastases in the lower left lobe. After 4 weeks, the patient was proposed for a contralateral surgical procedure. The postoperative evolution of the patient was good, without complications, with a good general condition. Testicular teratocarcinoma with multiple secondary determinations has a favourable prognosis if it benefits from radical resection of all tumours.

Renal dysfunction and its significance for the prognosis of retroperitoneal tumour patients

Angela Mădălina Lazăr, Eugen Brătucu, Claudiu Daha, Sânziana Ionescu

“Carol Davila” University of Medicine and Pharmacy Bucharest, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Radical surgery is regarded as the most important positive prognostic factor for retroperitoneal tumour patients. However, the radicalness of the surgical intervention is difficult to obtain due to the complexity and profoundness of retroperitoneal space, as well as tumour involvement of various important surrounding structures. Still, even after radical surgery, the overall survival of retroperitoneal tumour patients remains poor. There is no sufficient agreement on other factors that could be therapeutically controlled in order to improve the outcomes of surgery. In this context, the aim of the current study was to evaluate the impact of kidney function on patient prognostic. Patients and methods. We carried on an extended study on a group of 160 patients with retroperitoneal tumours who have been diagnosed and operated on in “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest, the First Surgical Clinic, over a period of 15 years. We analysed the frequency of patient preoperative organ dysfunctions, especially of renal dysfunction and its significance for the results of the surgical intervention and patient overall survival. Results. Preoperative kidney dysfunction, of various degrees, as assessed by blood tests, equations estimating glomerular filtration rate and medical imaging data, was found in 75% of the operated on patients. Renal dysfunction was associated to a lower rate of surgical radicalness, more operative complications and poorer overall patient survival. Also, it negatively influenced patient response to chemotherapy. Conclusions. As renal dysfunction, either pre-existing, or due to tumour progression, represents a negative prognostic factor for the surgical results, response to chemotherapy and patient survival rate, a thorough preopera­tive assessment of this function should be obtained. This assessment should­ include various tests in order to stratify correctly the degree of kid­ney dysfunction, guiding the selection of operable patients and an in­dividualized therapeutic approach.

Histopathological types of retroperitoneal sarcoma - is there any difference?

Angela Mădălina Lazăr, Eugen Brătucu, Claudiu Daha, Sânziana Ionescu

“Carol Davila” University of Medicine and Pharmacy Bucharest, “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Retroperitoneal tumours are known to be extremely aggressive tu­mours, difficult to resect completely and characterized by a pronounced tendency to local recurrence. More than 100 histopathological subtypes of sarcomas have been reported to develop in the retroperitoneal space, but there is conflicting data whether histopathological type presents a clear prognostic difference. In the present study we aimed to analyse the similarities and differences between different subtypes of retroperitoneal sarcomas in order to discover particulari­ties of evolution, response to treatments and overall prognosis. Patients and methods. We followed-up a group of 160 patients with retroperitoneal tumours who have been treated in “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest, the First Surgical Clinic, over a period of 15 years. We analysed several parameters including: the particularities of tumour localization and rate of progression, patient characteristics at admission, tumour vascularization and involvement of surrounding structures, type of surgery, perioperative complications and long-term evolution, all in correlation with tumour histopathological subtype. Results. There was an important heterogeneity in the histopathological type of retroperitoneal sarcomas. Contrary to some authors, we could not find a positive prognostic significance for well-differentiated liposarcomas, although their tendency towards local recurrence after surgery was obvious in our study too. Undifferentiated sarcomas associated the worst evolution, with low overall survival rates. Conclusions. A thorough knowledge on the particularities of different histopathological subtypes of retroperitoneal sarcomas is important in order to predict their response to therapies and to determine which patients should be initially treated by surgery and when radio- and chemothe­rapy should be the first therapeutic gesture. A precocious discrimina­tive attitude in the timing and schedule of therapies would be reflected in avoiding delays in effective treatment of sarcoma patients.

What role does surgery play in the treatment of carcinomatous mastitis?

Silviu Voinea, Angela Şandru, Cristian Bordea, Alexandru Blidaru

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Carcinomatous mastitis represents the most severe clinical form of breast cancer, with inflammatory phenomena and the overall increase in volume of the affected breast, usually with neoplastic invasion of the regional lymph nodes and remote metastases at the moment of establishing the definitive diagnosis. In front of this disarming picture, the initial treatment is systemic and consists in chemotherapy +/-hormonotherapy. For a positive response (disappearance of inflammatory phenomena, decrease in size of the affected breast and of adenopa­thies) if remote metastases are present, locoregional radiation therapy is continued in order to ensure a better local control. If there are no remote metastases and the inflammatory phenomena have disappeared after chemotherapy, surgery followed by irradiation may be performed. If the breast has ulcerations, superinfection or there is bleeding, toilet mastectomy may be performed even when remote metastases exist. The study batch is retrospective and includes 142 female patients with carcinomatous mastitis treated in the Institute of Oncology Bucharest during the period 1995-2000. In 42 cases (29.58%) at the moment of the definitive diagnosis there were already metastases (lymphatic, bone, lung, hematic, brain metastases). In all female patients the first therapeutic sequence was chemotherapy, associated with hormonotherapy (castration and Tamoxifen or Tamoxifen function of the menstrual status). Locoregional radiation therapy or of the remote metastases (bone, brain) was performed in 76 patients (53.52%). Surgical procedure was performed only in 52 cases (36.62%) and consisted in different mastectomy techniques: the Madden, Patey technique or mastectomy with lower axillary lymphadenectomy. The overall evolution of the batch was unfavourable with a survival at 5 years of only 40 cases (28.16 %) and at 10 years of only 7 cases (4.92 %), but female patients who had a favourable response to systemic treatment and who could be subject to surgery had an obviously higher survival rate than the other cases. For carcinomatous mastitis, surgery has a beneficial role, ensuring a better local control for the cases with a response to systemic treatment, and their evolution is significantly better compared to non-responsive cases. 

The importance of multiple lymphatic drainage in skin malignant melanomas

Silviu Voinea, Angela Şandru, Alexandru Blidaru

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Lately, the identification and biopsy of the sentinel node have become a standard in the treatment of malignant skin melanoma (MSM.) For the correct application of the technique and the reduction in the risk of false positive results it is compulsory to view the lymph drainage of the primary tumour by underlining all the sentinel nodes, regardless of their location. Method. At the “Prof. Dr. Al. Trestioreanu” Institute of Oncology Bucharest, lymphadenectomy has been performed during the last 3 years on 75 patients with malignant skin melanoma of stage I and II (AJCC). The primary tumour was located in the limbs in 39 of the cases and in the trunk in other 36 cases. In all patients lymphoscintigraphy was performed by intradermal injection of Nanocoll, by tracing in dynamics the migration of the radio tracer in order to capture the possible unusual locations of the sentinel nodes. Outcomes. Sentinel nodes were identified in all cases. For a number of 62 patients of the studied batch, the primary tumour drained within a single lymphatic basin, and in the other 13 it drained in two or more basins. The malignant melanomas in the trunk had a particular behaviour, having multiple drainage in a higher percentage compared to the ones in the limbs. Conclu­sions. Malignant melanomas of the trunk, especially the ones close to the median line, but not only those, have the tendency of draining in multiple lymphatic basins. The existence of the intermediate nodes and the atypical lymphatic drainage, in minor basins, should be underlined preoperatively in order to perform biopsies of all sentinel nodes and make the correct therapeutic decision.

Why do we discuss about surgery in the locally advanced stages of cervical cancer?

Silviu Voinea, Angela Şandru, R. Nicolăescu, Mircea Savu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Introduction. Both incidence and mortality caused by cervical cancer in Romania are the highest in Europa. Disease diagnosis in ad­vanced stages due to the lack of a national screening program is the main explanation for the increased rate of mortality. Due to the increasing number of patients needing radiation therapy and the small number of irradiation centres in our country, the treatment plan applied in Romania in the advanced stages of cervical cancer, IB2-III, differs to a certain extent from the one recommended in international guidelines. Mate­rial and method. Between January 2010 and January 2015, 150 female patients with cervical carcinoma in stages IB2 - IVA were treated within the Institute of Oncology Bucharest by the same multidisciplinary team. Following the staging of the disease through Rx or lung CT, abdominal-pelvic CT or MRI and cystoscopy, the female patients have been clas­sified as follows: IB2 - 17, IIA2 - 4, IIB - 111, IIIB - 15, IVA - 3. The treatment consisted in external irradiation in a dose of 50.4 Gy associated with concomitant chemotherapy with cisplatin weekly in a dose of 40 mg/m2. Irradiation was supplemented with two endocavitary applications, each with 7.5 Gy in point A, followed after 6-8 weeks by type II radical hysterectomy for female patients reconverted to being operable. Results. All patients were reassessed after a total irradiation dose in point A of 65 Gy and were considered operable. The histopathological result of the radical hysterectomy piece was a surprise: 68 female patients (45.3%) had the residual tumour in the cervix, while 5 of them also had this in the iliac nodes. The percentage of nonsterile pieces increased at the same time with the clinical stage of the tumour: 23.5% in stage IB2, 45.9% in IIB and 73.3% in IIIB. In the batch we followed-up, radiation therapy in a dose of 65 Gy in point A, a dose close to the one considered therapeutic by the majority of guidelines, of 80 Gy, succeeded in sterilizing the primary tumour only in 50% of the cases. Conclusions. Considering the high percentage of cases in which the persistence of the neoplastic cells was shown in irradiated tissue, and the reduced possibilities of the irradiation network in our country, we consider that the association of surgery with radiation therapy according to the described protocol is justified for the advanced cervical cancer.

Intra-arterial chemotherapy in cancers in the ENT area

Ioan Andrei, Anda Crişan, Florinel Bădulescu 

University of Medicine and Pharmacy of Craiova, Medical Oncology Discipline
Introduction. The key element which determined us to initiate a study regarding the assessment of the benefits of intra-arterial chemotherapy is the fact that, despite the therapeutic progress, the prognosis of ENT cancers is poor. The treatment of ENT cancers has raised many controversies, currently a therapeutic standard being represented by the concomitant radiation and chemotherapy with cisplatin. Materials and methods. A retrospective analysis of the studies pu­blished in the specialised magazines has demonstrated that intra-arterial chemoinfusion with cisplatin, concomitantly with radiation therapy, is better than intravenous administration from the perspective of the local tumour control and of tolerability. Because in the relapsing disease there are no studies assessing the benefits of the method, we intend to assess such in a female patient who deve­loped therapeutic failures in primary therapy. Conclusions. Intra-arterial chemoinfusion with cisplatin compared to the intravenous administration has proved its efficiency regarding the local tumour control and tolerability to treatment. In the relapsing disease, the ef­ficiency of intra-arterial chemoinfusion with cisplatin is clear, from the perspective of the safety profile, having good tolerability and of the activity profile, ensuring an improvement of the quality of life and an extension of survival through tumour regression, which is impos­sible to obtain with intravenous administration.

Psychosocial assistance in pediatric oncology

Alina Mitroi, Carmen Voiculescu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The improvement in the quality of life of the cancer patient and his/her family may be ensured through individualised planning of care from a social, psychological and educational point of view, the thorough understanding of the information regarding the disease, treatment and impact upon the family, the adaptation of the information at the level of understanding of the child, the support and encouragement of the child by all the members of the multidisciplinary team in order to remain active and have a life as normal as possible to the extent to which his/her special circumstances allow it. Once the treatment is completed, the multidisciplinary team makes sure that the patient is capable of being reintegrated at school and in society. The objectives of the psychological and social support in the field of oncopediatrics refer to the activation of the psychological and emotional resources in increasing adherence to treatment and the chances of social reintegration after completing the treatment, the increase in the level of information regarding the topic of oncopediatrics (treatment chances, diet, national and/or international medical institutions etc.), the increase in the material-financial power of the related family for the purpose of improving the patient’s response to treatment and the enrichment of the social support network who should support the patient’s needs.

Influence of using photon energy in the treatment of prostate cancer by using the 3D-conformational irradiation technique

M.A. Oprea1,2, L.E. Enciu1,2, G. Baranga1, L.R. Busuioc1,2, M. Croitoriu1, R. Stempurszki1, A. Constantinescu1, M. Savu1

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. University of Bucharest, Faculty of Physics, Măgurele
Medical physics has contributed substantially and still contributes to the progress in radiation therapy of prostate cancer. The purpose of this study is that of studying the effects of the photon beams with energy 6MV, respectively 15MV, regarding the planning of the target volume and of the critical organs in the case of prostate tumours. The study was performed on 10 patients. In order to facilitate the comparison between the energies used, the parameters were kept constant, and the results were interpreted on a dose-volume histogram (DVH). The comparison between the beams of different energies has shown differences in the analysis of multiple indices of homogeneity and compliance. The advantages and disadvantages of the energies used were analysed, regarding the doses collected from the risk organs and the optimization of the dose provided in the target volume.

Contact brachytherapy in the treatment of skin, perianal spinocellular carcinoma. Case study

Lucia Elena Enciu, Mădălina Croitoriu, Gabriel Baranga, Alexandru Oprea, Laurenţiu Busuioc, Doru Bășturescu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The spinocellular carcinoma is the most common malignant tumour of mucous membranes and the second most common from the perspective of frequency at skin level. The spinocellular carcinoma in the anogenital area manifests itself as a humid, red plate, with hard or ulcerating lesions. The associated symptoms include pain, itching and intermittent bleeding. This paper presents such a case, treated within the „Prof. Dr. Alexandru Trestioreanu” Oncology Institute, in the brachytherapy department. A 60-year-old female patient is irradiated through the brachytherapy technique, two times a week, with a dose of 300 cGy per session. For performing the irradiation, a moulding is made, so that the interest area is irradiated appropriately. Two treatment plans are drawn up. The first plan includes 6 applicators, of which­ 4 are loaded on a length of 7 cm, while 2 are loaded for a length of 3 cm. In this plan, the dose is normalised at a depth of 0.5 cm. The second plan contains 4 applicators loaded on a length of 3 cm and a normalisation of the dose at a depth of 1 cm. From the first plan, 30 Gy were administered to her, while from the second one - 15 Gy; in total - 45 Gy.

Progress in the systemic treatment of bronchopulmonary microcellular cancers

Miron Lucian 

Radiation Therapy and Medical Oncology Discipline, “Grigore T. Popa” University of Medicine and Pharmacy Iaşi, Clinical Oncology Clinic, Regional Oncology Institute Iaşi
Small-cell lung carcinoma (SCLC) represents 15% of all the bronchopulmonary cancers. SCLC is an aggressive form of the disease, with a rapid increase of the tumour, associated with smoking, with a different biology from the non-small-cell lung cancers. In SCLC, although very responsive to chemotherapy and radiation therapy (80%), the survival at 5 years is 6%, unchanged during the last 4 decades. Chemotherapy remains the main therapeutic method, and the combination of cisplatin and etoposide remains the unchanged standard treatment protocol. Relapse is very common in the extended stage of the disease, and the second-line treatment with cytostatics determines response rates of only 3-13%. Lately, once the molecular biology of SCLC has been decoded, new molecular therapeutic targets have been identified. It was proved that somatic mutations are very common in SCLC, determining the so-called “tobacco signature”: the loss of function of the suppressor genes p53, RB1 and amplifications of the MYC oncogene. Other anomalies noticed in SCLC include aberrations in the paths of repairing the DNA and changes in the NOTCH signalling path. All these have led to the assessment of the effect of some monoclonal antibodies targeted against the genetic alternations in SCLC. The modulation of the immune response represents another new method of treatment - currently, nivolumab, ipilimumab, pemrolizumab and durvalumab are assessed in clinical studies of phase II or III. The last molecular target identified in SCLC is DLL3 (Delta-like protein 3), and the monoclonal antibody conjugated with a cytotoxic agent Rovalpituzumab tesirine was associated with a spectacular response in a phase II study. SCLC are also characterised by the abnormal expression of the DNA repair proteins. The PARP activity is thus essential for the repair of the single strand breaks of the DNA. PARP inhibitors such as talazoparib, veliparib and olaparib are currently studied in association with cisplatin/etoposid or temozolamid in newly diagnosed patients or with relapsing SCLC. Conclusions. Little progress has been recorded in the treatment of SCLC during the last 40 years. The progress made in the last couple of years regarding the genomic and proteomic characterisation of neoplasia has identified new interesting therapeutic targets. The results of the current immunotherapy studies are optimistic; currently there are multiple studies regarding other new biological therapies for SCLC.

Interrelations of triple negative breast cancer in humans and animals

Antonela Bușcă, Marieta-Elena Panait, Mirela Dumitru, Sabin Cinca

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Cancer represents the second cause of mortality in humans and the first cause in dogs and cats. Malignant tumours occur spontaneously in pets which share the same living environment with humans and, consequently, are exposed to similar risk factors, so that they represent a special opportunity for compared oncology. Triple negative breast cancer (TNBC) is a form of cancer in which cells do not express on their surface estrogenic receptors (ER), progesteronic receptors (PR) or receptors of protein HER2. It is characterised through the increase and the development of metastases which is much faster than in other types of cancers and has a much higher rate of relapse, with a much more serious prognosis and a much lower survival rate. TNBC does not react to hormonal therapy or targeted therapy for HER2, which limits more the therapeutic options. Recent studies show that spontaneous malignant breast tumours in cats and dogs are similar to the human breast cancers regarding the pathology, tumour genetics and biologic behaviour; infiltrative breast cancer in female dogs seems to be more aggressive than the similar human form, and the feline mammary adenocarcinomas are characterised through a high degree of malignancy similar to the basal-like subtype of TNBC. Starting from these aspects, we can consider dogs and cats as excellent models for the study of the appearance of tumours in TNBC, due to the overall duration of life which is shorter in these animals, the high incidence which offers the possibility of analysing large samples of individuals, but also due to the faster progression of cancer in these species, which offers a much shorter response time. These characteristics may be extremely useful for the improvement of the diagnosis methods or for the development of much more efficient therapies, which may be subsequently transposed into the human oncological medical practice.

Persistent hyperantigenicity, a possible triggering factor for neoplasias in the immune cell system of humans and animals

Ana-Maria Coman, Daniela Frăţilă, Maria Alexandra Dumitru, Nicolae Manolescu 

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
The environment which allowed and determined the appearance of living beings conditions them and threats their existence permanently, so that the manner in which life unfolds is a result of the interaction between the organism and the environment, between heredity and nature. Thus, the aggression of the living environment upon the human being or animal manifests itself through the occurrence of pathological processes whose evolution is influenced by the reactivity of the cellular system of immunity (CSI). In this regard, there are multiple anatomical and clinical and experimental observations, started from the 1950s, demonstrating that one of the possible causes of lymphatic cancers is represented by the chronic aggression of hyperantigenicity induced by various etiologic agents of bacterial, viral, parasitic origin etc. which affects the homeostasis of the entire body through the involvement of the lymphoid tissues from the start of the evolution of the aggression. In this study we present briefly the stages of the cytomorphic transformation of a lymph node chronically aggressed persistently by the presence of polyparasitism at the level of vital organs, such as the liver and lung. 

Malignant proliferations of the plasmocitary line in dogs

Nicolae Manolescu1, Emilia Balint1, Daniel Lastofka2, Călin Chirilă2

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. “One Health - New Medical Concept” Association Bucharest
The study of specialised literature underlines certain interesting aspects regarding the problem of the plasmocytoma in the canine species. It is also noticed the unanimity of the veterinary oncology and pathology specialists who consider plasmocytoma a tumoral manifestation of the B lymphocytic cell line. The authors show aspects of malignant proliferations of the plasmocitary cell line encountered in dogs from the case studies of the veterinary clinics of the Bucharest Faculty of Veterinary Medicine. The anatomical and clinical forms investigated and diagnosed through cytomorphological examinations have been: splenic extramedullar plasmocytoma, lymph node extramedullar plasmocytoma, Waldenström lymphoma, Waldenström lymphoma with metastases in the pleural serosa, systemic Waldenström lymphoma, and plasma cell leukemia. The literature describes multiple locations of these cell proliferations, including multiple myeloma, which we did not identify in our cases. Instead, the bibliography studied did not refer to the existence in dogs of the Waldenström lymphoma and of plasma cell leukemia.

Biologic effects induced by peptides marked with 68Ga upon human and murine malignant cells

Elena Panait Marieta1, Livia Chilug2, Valentina Negoiță1, Antonela Bușcă1, Gina Manda3, Dana Niculae2, Mirela Dumitru1, Maria Iuliana Gruia1

1. “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
2. “Horia Hulubei” National Institute of Physics and Nuclear Engineering, Măgurele
3. “Victor Babeș” National Institute, Bucharest
The authors investigated possible biological effects induced by different peptidic compounds marked with 68Ga, proposed for being used in PET imaging upon human and murine malignant tumour cells. Materials and method. In this regard, 4 tumour cell lines used frequently in the in vitro experiments have been selected: glioblastoma (U87MG), colon carcinoma (HT-29), malignant melanoma (B16F10) and pancreatic carcinoma (AR42J). At the same time, peptides with known specificity to the cell receptors of the malignant lines mentioned above have been selected, namely: peptide of type Arg-Gly-Asp (RGD) (alpha (v)beta(3) integrin receptors, synthesis analogues of somatostatin: octreotide and octreotate (SST2) and Exendin-4 glycopeptide (GLP-1). The peptides marked with 68Ga as positron emitter through the bifunctional chelating agents represented by DOTA, NOTA or NODAGA, were put into contact with the line cells which overexpress the peptidic receptors. Apoptosis (using the set Abcam Annexin V-FITC/PI apoptosis detection kit), the proliferation index and the phases of the cellular cycle (BD CycleTestTM plus DNA kit) were measured through flow cytometry (FACSCalibur, BD Biosciences, USA). Outcomes. Peptides marked with 68Ga induced apoptosis and block the cells in the phase G2/M, for the lines U87MG and AR42J. Conclusions. The results suggest the usefulness of the imaging radiopeptidic agents for the early estimate of the response to the anti-cancer therapy. These results are also promising for continuing the in vitro and in vivo evaluation of radiopeptides, for the purpose of contributing to a better understanding of the radiobiologic mechanisms by showing cell changes associated with the medical imaging procedures. 

Analysis of expression of genes involved in proliferation, apoptosis and cell adhesion in colorectal cancer

Daniela Murăraşu, Corina-Elena Mihalcea, Sabin Cinca, Augustin Marincaş, Ciprian Cirimbei, Laurenţiu Simion, Liliana Puiu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
In the colorectal tumorigenesis process, there are multiple molecular events which change the expression profiles of certain genes involved in essential cell processes for the normal operation of the cell: cellular cycle and proliferation, apoptosis and cell adhesion. Protein p53 is the most important tumour suppressor and one of the most investigated molecular prognosis and prediction markers in the colorectal cancer (CRC); it transcriptionally regulates numerous genes or indirectly influences the activity of certain proteins. The purpose of the paper was the analysis of the expression of a set of 10 genes (TP53, TP53INP1, WRAP53, KLF4, EZH2, PLK1, BIRC5, SPARC, CDH1 and TACSTD1), involved in proliferation, apoptosis and cellular adhesion and which are linked to the activity of p53, the identification of molecular parameters useful in staging and prognosis of malignant diseases, as well as the correlations between the expression of these genes and the mRNA levels of TP53 in CRC. Materials and methods. Fourty fragments of tumour tissue and apparently normal adjacent mucous membranes collected from patients with CRC subject to surgery, within the “Prof. Dr. Alex. Trestioreanu” Institute of Oncology Bucharest have been analysed. From the samples, total RNA was isolated using Trizol (Thermofisher Scientific, USA), which was purified with the kit RNeasy Mini Kit 50 (Qiagen, Thermofisher Scientific) and reverse-transcribed in cDNA. The levels of tRNA of the 10 genes were measured through the semiquantitative detection of fluorescence in real time with the help of the device 7900 HT (Thermofisher Scientific) and of the pre-optimised probes TaqMan. The data obtained have been analysed with the programs SDS and RQ Manager 1.2 through the method ΔΔCt. The studies of correlation between the analysed parameters were performed with the program GraphPad Prism 5.0 (GraphPad Software Inc). Outcomes. In the CRC tumours, significant variations were noticed in the expression of the genes BIRC5, EZH2, PLK1, TP53, TACSTD1, CDH1, KLF4 and TP53INP1, when compared to normal tissue. The expression of the gene TP53 was correlated to the majority of the examined genes, except for CDH1, TACSTD1 and SPARC (in the normal tissues) and KLF4 and SPARC (in the tumour tissue). The increase in the expression levels of PLK1 and KLF4 was noticed in old patients and respectively in men. At the level of the tumours in the proximal colon, the decrease in the expression of CDH1 and TACSTD1 was noticed. Neoplasms with serous infiltration have been characterised by an increase in the expression of the genes CDH1, KLF4, TACSTD1 and TP53INP1 and a low expression of WRAP53, while the tumours at the level of the nodes have had a significant increase in the expression of the genes BIRC5, EZH2 and PLK1. At the same time, with the progression of the disease, the increase in the expression of the genes EZH2, TP53 and WRAP53 and the decrease in the expression of CDH1, KLF4 and TP53INP1 were noticed. In tumours with distal metastases, the expres­sion of the genes KLF4, SPARC and TP53INP1 decreased significantly, while the expression of TP53 increased. Conclusions. Except for SPARC and WRAP53, the expression of the other 8 genes analysed represents biomarkers for the CRC tumours confirmed in this study. The expression of the p53 tumour suppressor is highly correlated with the genes involved in cell proliferation. The levels of expression of the genes TP53, TP53INP1, KLF4 and CDH1 represent parameters which may be useful in the prognosis of the development of distal metastases. 

Ocular melanoma - from theory to medical practice

Daniela Zob, Dana Lucia Stănculeanu, Andreea Lăzescu, Mădălina Drăgănescu, Carmen Branzan, Cristina Ianculescu, Gabriela Murgoi, Ştefania Toma, Daniela Dascălu, Eliza Boncescu, Bogdan Laşcu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Ocular melanoma is a distinct entity with an increasing inci­dence in recent years. The incidence of ocular melanomas in the USA, ac­cording to Surveillance, Epidemiology and End Results (SEER), is 0.69/100,000 people per year in men and 0.54/100,000 people per year in women. Ocular melanoma has a particular prognosis and treat­ment. It represents 5% of all melanomas. Among ocular malig­nan­cies, melanomas are the most common. 13% of the deaths due to me­lanoma are caused by ocular melanoma because of the increased me­tas­tatic rate and poor response to treatment. Metastases occur in 31% of patients at 5 years, 45% at 15 years and 50% at 25 years, ac­cording to Collaborative Ocular Melanoma Study Group (COMS). Me­tastases in the liver are the most common - 89% of patients with me­tas­tasis. The death rate from metastasis is 80% at 1 year and 92% at 2 years. In recent years, the mutations that occur in ocular melano­ma and treatment options have been extensively researched. The re­sults obtained with various systemic therapies are disappointing. In this paper we intend to present prognostic factors and treatment mo­dalities.

Locoregional therapies in liver tumors 

Murat Dokdok

Anadolu Medical Center Hospital, Radiology Department, Kocaeli, Turkey
Altough surgery is curative, hardly one third of patients with HCC are suitable candidates for hepatic resection. Liver transplantation is the treatment of choice in a selected subset of patients, but this modality is plagued by the limited availability of donors. With regards to secondary tumors, only 25% of patients with colorectal metastases are candidates for surgery. Systemic chemotherapy has been shown to have limited therapeutic effects for primary and secondary hepatic malignancies, with low tumor response rates. Hence palliative management is the mainstay of therapy for most patients with primary and secondary liver tumors, most investigative efforts have now converged on local control. Loco-regional therapies as ablation and embolization are the two main groups in interventional oncology.

Cardiovascular effects of targeted molecular therapies and vascular toxicity of chemotherapy

Ştefania Toma, Dana Lucia Stănculeanu, Daniela Zob, Daniela Dascălu, Eliza Boncescu, Bogdan Laşcu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Targeted molecular therapy is the newest and most dynamic chapter of current oncology research, boosted by the recent complete decoding of the human genome. The most commonly used classes of molecular drugs currently include: small molecule tyrosine kinase inhibitors (TKI) and multikinase inhibitors, monoclonal antibody blocking transduction signals, angiogenesis inhibitors, proteasome inhibitors, histone deacetylase inhibitors and demethylation agents, epigenetic therapy, differentiation agents, gene therapy strategies and vaccines. Although targeted therapies are considered to be less toxic and better tolerated by patients compared to classical chemotherapeutic agents, rare but severe complications have been described, and longer follow-up is required to determine the exact profile and prognosis of associated cardiac adverse reactions. Both conventional chemotherapy and targeted molecular therapies are associated with well-defined short-term and long-term risks of cardiovascular events. Because these agents are commonly used for curative purposes, benefits maximization and concomitant reduction of cardiac risk have become a priority in oncology management, as well as monitoring to identify late toxicity.

Primary cytoreductive surgery or neoadjuvant chemotherapy in advanced ovarian epithelial cancer?

G.D. Subţirelu, A.M. Marincaş, C. Daha, C. Cirimbei, E. Brătucu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Ovarian cancer is the fifth most common cancer in women and the fifth leading cause of cancer death in women. Approximately 90% of ovarian primary malignancies have epithelial origin (carcinomas), and 70% of patients with ovarian epithelial cancers present with advanced stages, which raises major therapeutic problems. Advanced ovarian epithelial cancer (AOEC) treatment pillars are surgery and chemotherapy. Primary cytoreductive surgery (PCS) aiming at complete resection (R0) followed by chemotherapy based on platinum salts and taxanes was the standard treatment in AOEC. PCS results in AOEC are usually evaluated according to the amount of residual disease remaining after surgery: no macroscopic residual disease or optimal cytoreduction if residual tumors ≤1 cm or suboptimal cytoreduction if residual tumors >1 cm; but recent striking differences were observed between R0 and cytoreduction with macroscopic residual tumors (no matter their size), survival remaining significantly higher for patients with macroscopic residual tumors ≤1cm. Material and method. This is a retrospective study performed on a group of 389 patients with AOEC, operated between 2005 and 2014, at the 1st Department of General and Oncologic Surgery, “Prof. Dr. Alex. Trestioreanu” Institute of Oncology Bucharest. We examined each case with regard to the therapeutic sequence - PCS or neoadjuvant chemotherapy (NAC) and cytoreductive surgery, stage, histopathological type, the grade of differentiation, extent of surgery and its complications, the chemotherapy regimen administered. We evaluated the rate of R0 resections, the overall survival (OS) and the progression-free survival according to therapeutic sequence - PCS or NAC and cytoreductive surgery, stage, histopathological type, and tumor grading. Conclusions. We have noticed that OS of patients with neoadjuvant chemotherapy (NAC) was not inferior to that of patients with PCS, and postoperative morbidity at the time of cytoreduction was not higher in patients with NAC. Given that the goal of surgery in the AOEC is R0, it is still to be assessed if the PCS should be recommended in patients in whom we expect to obtain R0 and, on the other hand, to determine the sequence and the regimens for patients in whom we do not expect a R0 at the PCS.

The role of pelvic exenteration in locally advanced rectal malignancies

Claudiu Daha, Marian Marincaş, Ion Burlănescu, Vlad Rotaru, Ciprian Cirimbei, Elena Chitoran, Eugen Brătucu

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Despite efforts toward the early detection of rectal cancer, locally advanced primary colorectal cancer with involvement of adjacent pelvic organs is not uncommon. Pelvic exenterations represent major surgical procedures, having a mutilating character and for some patients with locally advanced rectal malignancies remain the only surgical curative or palliative treatment. The resectability of these tumors depends on the absence of lateral extension to the pelvic wall and iliac vessels or to sciatic foramen and also, on the absence of distant metastasis or paraaortic lymph node involvement. The study includes 11 the posterior pelvic exenterations performed for rectal malignancies in IOB (from a total of 106 pelvectomies), over a period of 9 years (2008-2016). Nine cases had radical intention and two were palliative. In 5 cases it was necessary the resection of the pelvic floor, and in two cases the resection of other extrapelvic organs.We mention the fact that two of the patients underwent posterior pelvic exenteration for two synchronous malignancies (cervical and rectal with vaginal invasion in one case, and ovarian and rectal cancer in the second one). The purpose of this paper is to evaluate the early and late results of the method. The perioperative mortality is low despite high postoperative morbidity. The overall survival of the patients operated with radical intent is comparable to that of data from the literature and better than other pelvic malignancies.

The advantages of contrast enhanced ultrasound (CEUS) in oncologic surgery

Simona Cirimbei, Raluca Buzatu, Alexandra Nicolăescu, Ciprian Cirimbei

“Prof. Dr. Alexandru Trestioreanu” Institute of Oncology Bucharest
Contrast-enhanced ultrasound (CEUS) has developed from the necessity to increase the sensitivity of standard ultrasound in the diagnosis of intraabdominal lesions, especially of hepatic tumors. Microbubble contrast agents allowed the descriptions of the hepatic lesions and other tumors, through their behaviors in three vascular phases - arterial phase, venous phase and parenchyma phase - and so, they can asses a certitude diagnostic with a sensitivity compared to CT or MRI exams. Objectives. In this study, we proposed to evidence the advantages of contrast enhanced ultrasound in oncologic surgery. Method. Eleven contrast enhanced ultrasound were performed in Surgery Department I of the “Prof. Dr. Alex. Trestioreanu” Institute of Oncology Bucharest, with Toshiba Nemio XG and Hitachi Aloca. Contrast enhanced used was Sonovue, a contrast enhanced of second generation. The lesions evaluated by contrast enhanced ultrasound usually have a perfusion pattern and acoustic amplification relative typical in vascular phases, which helped us to asses the diagnosis. Results. With contrast enhanced ultrasound, it was evaluated the response at RFA therapy of hepatic metastases in 6 patients known with digestive neoplasm. In two patients known with abdominal neoplasm, using contrast enhanced ultrasound, there were evidenced hepatic lesions which CT or MRI didn’t discover. In another two patients (one with prostatic nodular lesions, and the other with pancreatic lesions), the contrast enhanced ultrasound could establish with certitude that these lesions were benign. Conclusions. Contrast enhanced ultrasound is a safe and efficient method to explore the oncological surgical pathology. With contrast enhanced ultrasound, the diagnostic is rapid, with low costs compared with CT or MRI evaluation, and with the possibility to have a therapeutic attitude more quickly.

Molecular subtypes in male breast cancer

Laura Rebegea1,2, Dorel Firescu3,4, Cristina Șerban3,4, Mihaela Dumitru1, Mihaela Crăescu1,5

1. Department of Radiotherapy, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania 

2. Medical Clinical Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania
3. Surgery Clinic II, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galaţi, Romania 
4. Surgical Clinical Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania 
5. Morphopathological Sciences Department, Faculty of Medicine, “Dunărea de Jos” University of Galaţi, Romania
Male breast cancer (MBC) is a heterogeneous disease, being <1% from breast cancer, with differences respect median age at diagnosis, frequency of estrogen positive patients. Methods and material. This study involves 34 breast cancer male patients, diagnosed and treated in Oncology and Radiotherapy Department of „Sf. Ap. Andrei” Emergency Clinical Hospital, Galati for which there were available immunohistochemical tests (IHC) of 52 male breast cancer treated in our hospital in period: 1st January 1993 - 31st December 2016. Molecular subtype’s distributions and performed multimodal treatment were analyzed. Results. Median age of analyzed patients was 63 years old (range 45-79 years), with a greater frequency of 60-69 years old patients; a percent of 38.24% of cases presented IIIB stage of disease. Predominant histology was invasive ductal carcinoma in 88.24% of cases. Respect IHC, Luminal A molecular subtype was found in 64.71% of cases, Luminal B Her2-neu negative in 29.41%, luminal B, Her2-neu positive in 2.94%, and basal like in 2.94% of cases. Multimodal treatment involved surgery, external beam radiotherapy, chemotherapy and hormonal therapy (HT). HT with Tamoxifen performed 88.24% of cases. One patient developed, two years from breast cancer diagnosis, a second malignancy - prostate cancer. Histological characteristics respect molecular subtypes were analyzed but the statistical tests did not identify significant differences of parametric variance. Due to the high number of patients lost form follow up, we did not perform survival studies. Conclusions . Because the rarity of cases, MBC represents a specific subgroup in which the management principles are applied starting from therapeutically guides of female breast cancer. We notice a predominance of invasive ductal carcinoma histology, of Luminal A molecular subtype, with a higher frequency of Ki67<20% values, and grading G2. Over expression of Her2-neu is known as prognostic factor associated with low survival, in MBC. Low incidence of basal-like molecular subtype in MBC can be associated with high median age at diagnosis in men (66 years old) respect women and with low frequency of BRCA1 mutation in men.